Yang Yang

Zearalenone is a mycotoxin produced mainly by Fusarium. There are numerous incidences of mycotoxicosis in laboratory and domestic animals, especially in pigs. However, little is known about molecular mechanisms of zearalenone toxicity. Granulosa cells are the maximal cell population in follicles, and they play an essential role in the development and maturation of follicles. The objective of this study was to explore the effect of zearalenone at high concentrations on proliferation and apoptosis of porcine granulosa cells and uncover signaling pathway underlying the cytotoxicity of zearalenone. We found that zearalenone reduced the proliferation of porcine granulosa cells in a dose-dependent manner as shown by the MTT assay and zearalenone resulted in an obvious apoptosis and necrosis in porcine granulosa cells as determined by the TUNEL analysis and flow cytometry. In addition, TUNEL assay with caspase inhibitors showed that zearalenone triggered a caspase-3- and caspase-9-dependent apoptotic process in porcine granulosa cells. Fluorescence spectrophotometer displayed that zearalenone led to a loss of mitochondrial transmembrane potential of porcine granulosa cells but enhanced reactive oxygen species (ROS) levels of the cells. Notably, Western blots revealed that caspase-3 and caspase-9 were activated by zearalenone in porcine granulosa cells. Collectively, our results suggest that zearalenone induces apoptosis and necrosis of porcine granulosa cells in a dose-dependent manner via a caspase-3- and caspase-9-dependent mitochondrial pathway. This study thus offers a novel insight into molecular mechanisms by which zearalenone has adverse cytotoxicity on reproduction.

Ulcerative colitis (UC) is a chronic and etiologically refractory inflammatory gut disorder. Although berberine, an isoquinoline alkaloid, has been revealed to exert protective effects on experimental colitis, the underlying molecular mechanism in chronic intestinal inflammation remains ill-defined. This study was designed to uncover the therapeutic efficacy and immunomodulatory role of berberine in chronic UC. Therapeutic effects of oral administration of berberine were investigated in dextran sodium sulfate (DSS)-induced murine chronic UC and the underlying mechanisms were further identified by si-OSMR transfection in human intestinal stromal cells. Berberine significantly attenuated the experimental symptoms and gut inflammation of chronic UC. Berberine treatment could also maintain the intestinal barrier function and rectify tissue fibrosis. In accordance with infiltrations of antigen-presenting cells (APCs), innate lymphoid cells (ILCs), and activated NK cells in colonic lamina propria, increased expression of OSM and OSMR were observed in the inflamed tissue of chronic UC, which were decreased following berberine treatment. Moreover, berberine inhibited the overactivation of human intestinal stromal cells through OSM-mediated JAK-STAT pathway, which was obviously blocked upon siRNA targeting OSMR. The research provided an infusive mechanism of berberine and illustrated that OSM and OSMR intervention might function as the potential target in chronic UC.

An outbreak of urinary stones associated with consumption of melamine-tainted milk products occurred in 2008 in China, leading to serious illness of many infants and even death. However, the toxicity of melamine in kidney epithelial cells remains unclear. We have explored the effects of melamine and trolox on renal NRK-52e (normal rat kidney 52e) cells. The IC(50) of melamine was measured by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] assay. Total SOD (superoxide dismutase) was determined by NBT (Nitro Blue Tetrazolium) staining method. GSH-Px (glutathione peroxidase) activity was detected by UV colorimetric assay, and MDA (malondialdehyde) content was determined by thiobarbituric acid assay. Apoptosis induced by melamine was determined by flow cytometry. The IC(50) increased when NRK-52e cells were treated with both melamine and trolox compared with melamine only. SOD and GSH-Px activities were decreased, but MDA content was increased by melamine in a dose-dependent manner. Trolox significantly enhanced SOD and GSH-Px activity in melamine-treated NRK-52e cells, but it decreased their MDA content. LDH (lactate dehydrogenase) activity and the level of ROS (reactive oxygen species) of the NRK-52e cells were enhanced by melamine compared with the control. Furthermore, the apoptosis rate increased in NRK-52e cells treated with melamine, whereas trolox was protective. These results show that melamine has an obvious adverse effect on proliferation of NRK-52e cells, causing oxidative damage and apoptosis, thus providing a novel insight into renal cytotoxicology of melamine. Trolox ameliorates the effect on melamine toxicity.